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Published ahead of print on February 2, 2006, doi:10.1164/rccm.200511-1789OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 10, May 2006, 1155-1160

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Submitted on November 22, 2005
Accepted on January 27, 2006

Soluble Mesothelin-related Protein in the Diagnosis of Malignant Pleural Mesothelioma

Arnaud Scherpereel1*, Bogdan D Grigoriu2, Massimo Conti3, Thomas Gey4, Marc Gregoire5, Marie-Christine Copin6, Patrick Devos7, Bachar Chahine4, Henri Porte3, and Philippe Lassalle8

1 INSERM Unit 774, Institut Pasteur de Lille, Lille, France; Pulmonary and Thoracic Oncology Department, University Hospital of Lille, Lille, France, 2 INSERM Unit 774, Institut Pasteur de Lille, Lille, France; Department of Pulmonary Medicine, University of Medicine, Iasi, Romania, 3 Thoracic Surgery Department, University Hospital of Lille, Lille, France, 4 Pulmonary and Thoracic Oncology Department, University Hospital of Lille, Lille, France, 5 INSERM Unit 601, University Hospital of Nantes, Nantes, France, 6 Pathology Deparment, University Hospital of Lille, Lille, France, 7 Department of Biostatistics, Medical School of Lille, Lille, France, 8 INSERM Unit 774, Institut Pasteur de Lille, Lille, France

* To whom correspondence should be addressed. E-mail: a-scherpereel{at}chru-lille.fr.

Background: Diagnosis of malignant pleural mesothelioma is a challenging issue. Potential markers in mesothelioma diagnosis include soluble mesothelin-related peptides (SMRP) and osteopontin but no subsequent validation have been published yet. Methods: We prospectively evaluated SMRP in serum and pleural effusion from patients with mesothelioma (n=74), pleural metastasis of carcinomas (n=35), or benign pleural lesions associated with asbestos exposure (n=28), recruited when first suspected for mesothelioma. Findings: Mean serum SMRP level was higher in mesothelioma (2.05 ± 2.57 nM/l - median ± interquartile range) than in metastasis (1.02 ± 1.79 nM/l) or benign lesions (0.55 ± 0.59 nM/l) patients. The area under the receiver operating characteristic curve (AUC) for serum SMRP was 0.872 for differentiating mesothelioma and benign lesions; cut-off= 0.93 nM/l (Sensitivity= 80%, Specificity= 82.6%). The AUC for serum SMRP differentiating metastasis and mesothelioma was 0.693; cut-off= 1.85 nM/l (Sensitivity = 58.3%; Specificity = 73.3%). SMRP values in pleural fluid were higher than in serum in all groups (mesothelioma: 46.1 ± 83.2 nM/l; benign lesions: 6.4 ± 11.1 nM/l; metastasis: 6.36 ± 21.73 nM/l). The AUC for pleural SMRP differentiating benign lesions and mesothelioma was 0.831; cut-off= 10.4 nM/l (Sensitivity = 76.7%, Specificity = 76.2%). The AUC for pleural SMRP differentiating metastasis and mesothelioma was 0.793. Interpretation: We show that SMRP may be a promising marker for mesothelioma diagnosis when measured either in serum or pleural fluid. The diagnostic value of SMRP was similar in both types of samples, but pleural fluid SMRP may better discriminate mesothelioma from pleural metastasis.
Key words: pleural disease, neoplasm, marker, diagnosis




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